PROJECT SUMMARY: Research Project 1 The University of Georgia?s (UGA) Center for Translational and Prevention Science (CTAPS; P20 MH068666, P30 DA027827) has been funded continuously since 2003 to advance next-generation basic and preventive investigations of risk, resilience, and drug use among African American young people living in resource poor communities. The CTAPS P50 proposal is based on the hypothesis that progress in the prevention of drug abuse and cardiometabolic disease among African Americans requires consideration of the processes through which chronic, multigenerational poverty and social adversity become embedded in biological and behavioral systems in ways that confer heightened vulnerability to addictive behaviors. Conceptually, the Center?s research program is grounded in a neuroimmune network (NIN) model authored by Center scientists that highlights bidirectional signaling between the brain and immune system in the pathophysiology of addictive behaviors. The NIN model proposes that chronic stressors amplify crosstalk between peripheral inflammation and neural circuitries subserving emotion generation and regulation. This crosstalk results in chronic low-grade inflammation, which upon accessing the brain, accentuates threat processing in cortico-amygdala circuity, attenuates reward processing in cortico-striatal circuity, and dampens prefrontal executive control. NIN dysregulation is hypothesized to predispose individuals to substance misuse and high fat diets, in part, to self- medicate the negative emotions associated with disrupted neural signaling. These behaviors generate additional inflammation, as well as neuroadaptive changes in reward circuitry, further elevating risk for substance misuse. In Research Project (RP) 1, we propose one of the first prospective studies to test NIN predictions from a sample of 225 African American youth. Participants will be ages 18-19 at study enrollment, a period of time in which substance use and unhealthy eating rapidly escalate among African Americans. At Time 1 (T1) and T2 (2.5 years later), participants will complete a blood draw to quantify low-grade inflammation, fMRI scanning of threat-, reward-, and executive control neural activity, and assessments of stress exposure, addictive behaviors, and cardiometabolic risk. RP1 integrates research on multiple organ systems (i.e., brain and immune system) to advance the science of risk and resilience for addictive behaviors and their cardiometabolic health consequences, especially among low income African American communities and other US populations exposed to chronic stress.